Definition of Terms
TOF: Time-of-flight mass spectrometer.
Multi-reflection: A TOF with more than one reflector (also called reflectron) is referred to as a multi reflection TOF.
Multi-path: A TOFMS where one ion path is followed multiple times is referred to as a multi-path TOF.
V-path: V-shaped path of ions in a TOF. This is currently the most common path in TOFs. Ions start in the extraction, fly down to the reflector and then up to the detector.
W-path: W-shaped path of ions.
I-path: With an I-shaped ion path, the ions always fly along the same axis.
Isochronous oscillation: An ion oscillation whose frequency is independent of the ion energy is referred to as an isochronous oscillation.
Time-of-flight: The time it takes an ion to transverse one (or several) ion optical elements. In general, this time is a function of the initial properties of the ion:T=T+(K, Y, Z, A, B)  (1) Where K is the initial kinetic energy of the ion, Y and Z are the initial positions of the ion and A and B define the initial direction of the ion's motion. For convenience the above function is often transformed to a coordinate system defined by some reference ion. The time-of-flight function is thenT=T+(δ1, y1, z1, α1, β1)  (2) Where δ=(KR−K)KR=ΔK/KR is the initial kinetic energy difference relative to the reference ion kinetic energy KR, y and z define the initial position relative to the reference ion, and α and β define the initial direction relative to the reference ion. The Taylor expansion of this function is:T+(δ,y,z,α,β)=T0+(∂T/∂δ)δ+(∂T/∂y)y+(∂T/∂z)z+(∂T/∂α)α+(∂T/∂α)α+(∂T/∂β)β+terms of higher order  (3) 
This is often written asT+(δ,y,z,α,β)=T0+(T/δ)δ+(T/y)y+(T/z)z+(T/α)α+(T/β+terms of higher order  (4) T0 denotes the time-of-flight of the reference ion, whereas the sum of all other terms is called the time error ΔT of the ion under consideration caused by its initial conditions. For now we look at an ion that starts at the same position with the same direction as the reference ion, hence y=z=α=β=0. We also assume that this ion (as the reference ion) moves on the axis of an axial symmetric ion reflector. Because of symmetry reasons, this ion will stay on the axis and we get:T(δ)=T0+(∂T/∂δ)δ+(∂2T/∂δ2)/2δ2+(∂2T/∂δ2)/6δ3+  (5) Or in the short notation:T(δ)=T0+(T/δ)δ+(T/δ2)δ2+(T/δ3)+ . . . T0+ΔT  (6) ΔT(δ)=(T/δ)δ(T/δ2)δ2+(T/δ3)δ3+  (7) 
Time focusing: An ion optical system with (T/δ)=0 is called first order time focusing. If in addition (T/δ2)=0 then it is called second order time focusing, and so on.
Dispersion: In this patent we only consider time dispersion. The time dispersion of an ion traversing an ion optical element is the time error caused by energy deviation ΔT(δ) that this ion has relative to some reference ion. In a perfectly isochronous system, per definition, this dispersion is ΔT(δ)=0. A fieldless drift section has a negative dispersion, meaning that ions of higher energies will require less time to traverse the system than the reference ion. An ion reflector may have a negative or a positive dispersion and, if adjusted correctly, can compensate the negative dispersion of a drift section so that the combination of the two become an isochronous system.
Reflectron: An ion reflector with positive dispersion, which is able to compensate to second order the dispersion of a drift tube.
FRT: Fourier reflectron trap, the instrument disclosed in this patent.
1. Field of Invention
The invention is a mass spectrometer (MS), a method for qualitative and/or quantitative chemical and biological analysis. It is a merger of an ion trap (IT) MS and a time-of-flight (TOF) MS.
2. Description of Prior Art
The ion reflector for compensation of time errors in TOFs was first proposed by Alikanov in 1957. In 1973 a US patent for such a device was granted to Janes U.S. Pat. No. 3,727,047. A two-stage ion reflector (reflectron) was proposed by Mamyrin in 1966 in order to increase the resolving power of their instrument, Mamyrin et al, U.S. Pat. No. 4,072,862. The two stages allowed for second order time error compensation in combination with a drift section. Grids of high transparency were used to obtain two stages of linear fields. Such a two-stage reflector allows obtaining a total ion flight path of good isochronous quality in a TOF.
Later, a godless reflectron was developed by Frey et al., U.S. Pat. No. 4,731,532, in order to reduce the loss of ions. This gridless reflector consisted of coaxial rings. In most cases, the electric potential of those rings are chosen in a way that generates two sections of more or less linear fields on the axis of the reflector. In order to compensate the defocusing properties of such a gridless reflector, a focusing lens is added in front of the reflector. This so-called reflector lens may be an accelerating or a retarding lens. Because accelerating lenses produce smaller time errors to the time-off-light of the ions, mostly accelerating lenses are used.
Gridless reflectors require a set of rings and many adjustable voltages to regulate the voltages of these rings. In order to facilitate the construction, reflectors from resistive films or materials were introduced. Another approach replaced the ring structure with conductive traces on PCB boards.
Time-of-flight mass spectrometers with multiple reflections were suggested rather early in 1990, see Wollnik and Prezewloka, Time-of-Flight Mass Spectrometers with Multiply Reflected Ion Trajectories, International Journal of Mass Spec. and Ion Processes, 96 (1990) 267-247, but their popularity grew only in the last few years. A W-shaped path was presented by the University of Bem in 1998 (S. Scherer et al., Prototype of a Reflectron, time-of-flight mass spectrometer for the Rosetta rendevous mission, Proc. 46th ASMS Conference, Orlando, Fla., 1998, p. 1238), and then was also incorporated in a commercial instrument by Micromass in 2000 (H. Bateman et al., Micromass, Proc. 48th ASMS Conference, Long Beach, Calif., 2000). Simultaneously, the Wollnik group started to design instruments where ions make multiple reflections passing a V-shaped path several times (H. Wollnlik et al., 47th ASMS Conference, Dallas, Tex., 1999). In 1999, a group from University of Uppsala presented a multi reflection I-path Maldi-TOF that used grided reflectors and electron multipliers (C.K.G. Piyadasa et al., A High Resolving Power Multiple Reflection, MALDI TOF, Rapid Commun. Mass Sprectrom. 13, 1999, p. 620-624). This instrument was designed to analyze a population of ions. In 1999 Hanson presented an I-path multi reflection instrument with a wire guide and grided reflectors (C. D. Hanson, 47th ASMS Conference, Dallas, Tex.,1999). In 2000, the group of Wollnik presented an I-path instrument with gridless reflectors (Wollnik et al., 48th ASMS Conference, Long Beach, Calif., 2000), and at the same time Brucker Daltonics presented a commercial ESI instrument with I-path multi-reflection using a grided reflector (Melvin Park, Brucker Daltonics, Inc., 48th ASMS Conference, Long Beach, California, 2000).
Some of those I-path TOFs have resolving powers mrnAm of several times 10'000. The drawback is that the useful mass window gets more and more restricted, as more multiple paths are done. One method to overcome this limitation has been presented by Makarov in 1999 (Makarov, HD Technologies, 47th ASMS Conference, Dallas, Tex., 1999): he built an isochronous ion trap (Orbitrap) using only a static electric field. Static electric fields may not be used to trap ions at rest, but if the ions have sufficient kinetic energies and the correct starting conditions, it is possible to trap ions with static electric fields. Seeing Makarov's ion trap, I realized, that isochronous reflectors as used in TOFs can also be used make an electrostatic isochronous ion trap, where the oscillation frequencies of the ions are sensed by a pick up electrode.
Already in 1994, Strehle patented an electrostatic ion trap with two opposing reflectors, an I-shaped flight path and an image charge detector, sensing the ion oscillations in the trap. As in the Makarov trap, the Fourier Transform of this signal would yield the ion oscillation frequencies. From those frequencies the ion masses can easily be calculated. This instrument was very innovative, because it did not use an electron multiplier detector as TOFs usually do, but it used a tubular pick up electrode to sense the repetitive, induced signal from the trapped ion passing through this electrode.
In 1997, the group of Prof. Benner used a similar instrument in order to determine the mass, charge and velocity of large individual ions (W. H. Benner, Anal Chem. 69, 1997, p. 4162-4168). However, there were some fundamental differences to the instrument taught by Strehle:                a) Benner did not use isochronous reflectors, hence his trap worked best with only one ion oscillating in the trap. Using several ions (of the same specie) would have lead to a temporal dispersion of those ions because it is not possible to generate all ions monochromatically (with the same energy). The lack of isochronity would have degraded the signal, thus preventing the measurement with high resolving powers. This lack of isochronity, however, did not play a role in the experiments he was interested in, namely the detection of mass and charge of extremely large multiply charged ions.        b) The pick up transient was not Fourier transformed in order to get the mass spectrum. Instead, the oscillation time of the ion in the trap was determined by measuring the time difference between the pick up signal peaks. In order to get reliable measurements, these peaks hence had to be quite much larger than the electronic noise. Therefore, only multiply charged ions could be measured with this instrument. Also, only few ions of different species could be measured simultaneously so that the pick-up signal of those ions were not confused. The amplitude of the pick up signal was used to measure the charge state of the ion.        
In 1999 A.L. Rockwood from Sensar Larsen-Davies Corp. published an article (A.L. Rockwood, Journal American Society Mass Spectrometers, 10/3 (1999), p. 241) where he recognized that the Benner trap could be used for the analysis of several ions if the reflectors could be made isochronous. He presented simulations that showed a resolving power of up to 6000 for an ion package making several reflections, using very simple first order time focussing reflectors. In his paper, however, he did not discuss injection and detection of the ions.
The possibility to store ion packages in an electrostatic reflector trap was also demonstrated by Zajfman et. al. in 1996 (D. Zajfman et al., Phys. Rev. A 55/3, 1997, p. R1577). In July 2000, this group changed its storage trap into an isochronous reflectron trap and demonstrated quite high resolving power (Ring, H. B. Pedersen, O. Heber, M. L. Rappaport, P. D. Witte, K. g. Bhushan, N. Altstein, Y. Rudich, I. Sagi, and D. Zajfman; Fourier Transform Time-of-Flight Mass Spectrometry in an Electrostatic Ion Beam Trap: Anal. Chem. 72 (2000) p. 4041-4046) using EI and MALDI.